Perturbation of the smooth muscle cells (SMC) in the vascular wall, resulting in proliferation and migration, is the basic cause of fibrous/fibrofatty accumulation and intimal thickening, i.e., atherosclerosis, the major cause of vascular disease. In order to understand the biology of the SMC and the physiological basis for the sudden changes in the phenotype of the media] SMCs, we propose to investigate the molecular biology and kinetics of single SMCs from rabbit vascular tissue under normal and experimentally induced pathological conditions. This information will help us understand the kinetic properties of individual SMCs and the contractile protein myosin isoform composition in physiological and pathological (atherosclerosis) conditions. As a prelude to understand the cellular biology of medial SMCs that form the intimal thickening in atherosclerosis, we propose to determine: a) the distribution of the different types of SMCs along the arterial tree in the context of their mechanical properties, b) possible correlations between the kinetics of SMC mechanics and the diversity in the molecular composition of the contractile machinery, and c) changes in these properties under experimentally induced pathological conditions. Specifically, we propose to study the physical and mechanical properties (i.e., cell size, unloaded shortening velocity, extent of shortening, force production) of the same arterial smooth muscle cell. The specific aims of this investigation are to determine: 1) the diversity of SMC types in terms of myosin isoform composition in different regions of the arterial wall, 2) correlation of myosin isoform composition with the variations in cell mechanics, 3) if the myosin heavy chain (MHC) and myosin light chain (MLC) isoforms are coordinately regulated, and 4) if any of the specific medial wall cell types are selectively more prone to migration and proliferation (resulting in intimal thickening) with perturbation of the endothelial wall. The results obtained in these studies will throw light on the cellular origin of the atheroma.